- Explain to interested patients that this study suggests that air pollution may raise the risk of asthma through changes to a gene involved in immunity and inflammation, researchers found.
- Note that the observational study could not prove causality.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
NEW ORLEANS — Air pollution may raise the risk of asthma through epigenetic changes to a gene involved in immunity and inflammation, researchers found.
People with asthma who live in an area with heavy air pollution had significantly greater methylation of the Foxp3 gene compared with those living where the air is cleaner, according to Cameron McDonald-Hyman, MD, of Stanford University, and colleagues.
Methylation impairs expression of the gene and thus suppresses regulatory T cells’ ability to control inflammation in asthma "resulting in severe asthma and allergies," they reported at the American Academy of Allergy, Asthma & Immunology meeting.
Changes to the genome that occur without an alteration to the DNA sequence but have an impact on their expression are increasingly recognized as a route through which the environment affects disease susceptibility, according to a panel of leading asthma and allergy specialists at a press conference here.
Paying attention to air pollution and other alterations of the environment has become more crucial with the discovery that these epigenetic changes can be passed on to the next generation, Gurjit K. Khurana Hershey, MD, PhD, of Cincinnati Children’s Hospital, said.
Children are particularly vulnerable to the effects of air pollution and other environmental exposures, which the World Health Organization estimates cause more than a third of diseases in children under age 5.
So the researchers studied four cohorts of California children for the epigenetic impact of air pollution exposure.
One particularly hard-hit area in California is the city of Fresno, where 34% of children have asthma between ages 5 and 17 — nearly twice the state average of 18%.
A cohort of 68 Fresno kids ages 8 to 18 with asthma and exposure estimates for important pollutants and allergens were included in the analysis along with 10 age- and sex-matched healthy controls from Fresno.
They were compared with another 40 matched children (half with asthma and half without) from a suburb near Stanford in the San Francisco Bay area where state monitoring shows better air quality.
Small airborne particulate matter is more than twice as high in downtown Fresno than in Stanford. Polyaromatic hydrocarbon levels are roughly 30 times higher in Fresno, which also exceeds state air quality standards for ozone 86 days a year.
All three of these air pollutants have been linked to inflammation in the lung, McDonald-Hyman noted.
His group found the suppressive function of regulatory T cells in blood samples from the Fresno asthmatic children was roughly half that of controls in the low air pollution area on average.
Fresno controls were second lowest on regulatory T-cell function, followed by Stanford asthmatics and Stanford controls. All were significantly worse than Fresno asthmatics, though (all P≤0.01).
"We really think this is attributable to some sort of dysfunction in the regulatory T cells," McDonald-Hyman said, citing the lack of differences between groups in CD4+ T cell proliferation.
Staining of these regulatory T cells for Foxp3 expression showed the same pattern of significantly lower levels in children with asthma, again lowest in those from Fresno (all P≤0.05).
Fresno asthmatics also carried more methylation of Foxp3 gene regions than Fresno controls (P≤0.01), Stanford asthmatics (P≤0.001), or Stanford controls (P≤0.001).
"We see at all three levels from function to expression to the DNA level that there’s a significant difference in Fresno asthmatics," McDonald-Hyman said at the session.
He noted that degree of Foxp3 methylation was also tied to asthma severity among the children with asthma.
But the observational study could not prove causality, he cautioned.
And although the researchers tried to control for factors such as tobacco smoke exposure, ethnicity, socioeconomic status, and diet, they didn’t have data on medical history, viral infection, and other important possible confounders.
Another important factor that is still emerging is an individual’s "biologic dose" rather than the community "exposed dose," said Khurana Hershey.
Two people exposed to the same amount of pollution may be affected differently based on their individual genetic susceptibility, she said at the press conference.
The study was funded by an AAAAI award, the Westly Foundation, McCormick Award, Austin Memorial Award, the Stanford Center for Environmental Health Studies in Children, P20 award, NIEHS, and the Mary Hewitt Loveless Foundation Award.
McDonald-Hyman reported no conflicts of interest.
Khurana Hershey reported no conflicts of interest.
American Academy of Allergy, Asthma & Immunology
McDonald-Hyman C, et al "Epigenetic modifications of Foxp3 locus are associated with asthma in children exposed to high levels of ambient air pollution" AAAAI 2010; Abstract L2.